Pyridine → 1,1-Dimethylethyl (1-{[(1R)-3,8-dioxo-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylen-1-yl]methyl}-4-piperidinyl)carbamate

HRID 420702Notes

Reaction equation

HRID 420702 reaction equation
CS(O[CH2:6][C@H:7]1[N:17]2[C:18]3[N:9]([C:10](=[O:20])[CH:11]=[N:12][C:13]=3[CH:14]=[CH:15][C:16]2=[O:19])[CH2:8]1)(=O)=O.N1C=CC=CC=1.[NH:27]1[CH2:32][CH2:31][CH:30]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:29][CH2:28]1>CC#N>[O:20]=[C:10]1[CH:11]=[N:12][C:13]2=[C:18]3[N:9]1[CH2:8][C@@H:7]([CH2:6][N:27]1[CH2:28][CH2:29][CH:30]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:38])([CH3:37])[CH3:39])[CH2:31][CH2:32]1)[N:17]3[C:16](=[O:19])[CH:15]=[CH:14]2

Participants

5

Reactant 3

HCID 1049Pyridine2×HCID 7238334-(N-Boc-amino)piperidine2×HCID 58001764[(1S)-3,8-Dioxo-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylen-1-yl]methyl methanesulfonate

Product 1

HCID 866368431,1-Dimethylethyl (1-{[(1R)-3,8-dioxo-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylen-1-yl]methyl}-4-piperidinyl)carbamateYield 40.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

A solution of [(1S)-3,8-dioxo-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylen-1-yl]methyl methanesulfonate (1.05 g, 3.53 mmol) in dry CH3CN (50 ml) at room temperature under argon was treated with pyridine (0.343 ml, 4.24 mmol), followed by 1,1-dimethylethyl 4-piperidinylcarbamate (0.884 g, 4.24 mmol). The mixture was heated at 70° C. for 1.5 h and then at 90° C. for 3 h. LCMS showed ˜25% of product. So 0.5 eq of pyridine and 0.5 eq of 1,1-dimethylethyl 4-piperidinylcarbamate were added and the reaction was heated at 90° C. overnight and then stirred at room temperature for 2 days. The reaction was complete. The solvent was evaporated and the residue partitioned between sat NaHCO3 and 20% MeOH/DCM (100 ml/100 ml). The layers were separated and the aqueous layer was extracted with 20% MeOH/DCM again (2×100 ml). The combined organic extracts were dried over MgSO4, filtered and evaporated to afford 1.7 g of crude which was purified by silica chromatography using a 0-5% MeOH/DCM gradient to afford the product as a yellow solid (0.57 g, 40.2%).

Workup

  1. temperaturethe reaction was heated at 90° C. overnight
  2. customThe solvent was evaporated
  3. customthe residue partitioned
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with 20% MeOH/DCM again (2×100 ml)
  6. dry with materialThe combined organic extracts were dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto afford 1.7 g of crude which
  10. customwas purified by silica chromatography

Sources & evidence

ORD record
ord-f224ed78d9ab47a3a1464a07a2c06638
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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